Large Intestine, Constipation and Lactose Intolerance

What type of muscle is responsible for GI motility?

Usually due to smooth muscle (circular, longitudinal layers and the muscularis mucosa), but skeletal muscle also important in the mouth, pharynx, upper oesophagus and external anal sphincter.

What type of neurons are present in the enteric nervous system?

Sensory neurons (mechanoreceptors, chemoreceptors, thermoreceptors).

Interneurons (co-ordinating reflexes and motor programs).

Effector neurons ( excitatory and inhibitory motor neurons).

Describe the parasympathetic nervous system of the GI.

Preganglionic fibres (releasing ACh) synapse with postganglionic neurones within the enteric nervous system.

Excitatory influences in the GI parasympathetic nervous system cause increased gastric, pancreatic and small intestinal secretion, blood flow and smooth muscle contraction.

Inhibitory influences in the GI parasympathetic nervous system cause relaxation of some sphincters, receptive relaxation of the stomach.

Describe the sympathetic nervous system of the GI.

Preganglionic fibres (releasing ACh) synapse in the prevertebral ganglia. Postganglionic fibres (releasing noradrenaline) innervate mainly enteric neurones. It is functionally less important than the parasympathetic division.

Inhibitory influences cause decreased motility, secretion and blood flow.

How are hundreds of GI cells able to contract at the same time?

Adjacent smooth muscle cells are coupled by gap junctions, which electrically couples adjacent cells, allowing the spread of electrical currents from cell to cell forming a functional syncytium, so hundreds of cells are depolarised at the same time.

Describe how the basic electrical rhythm in the GI is formed.

Smooth muscle spontaneous activity occurs as slow waves, which is rhythmic patterns of membrane depolarisation and repolarisation that spread from cell to cell via gap junctions. Slow waves are driven by the interstitial cells of Cajal (ICCs), which are pacemaker cells located between the longitudinal and circular muscle layers and in the submucosa. Contraction occurs when slow wave amplitude is sufficient enough to trigger action potential. These slow waves determine the basic electrical rhythm (BER).

What is the BER frequency in different areas of the GI tract?

Stomach- 3 slow waves per minute.

Duodenum- 1-12 waves per minute.

Terminal ileum- 8 waves per minute.

Describe peristalsis and its purpose.

A series of wave-like muscle contractions that move food through the digestive tract, triggered by distension of the gut wall. This involves contraction of longitudinal muscle layers.

What is tonic contraction?

Sustained contractions found in the sphincters of the GI tract.

What is segmentation?

Rhythmic contractions of the circular muscle layer that mix and divide luminal contents.

What are the 5 principle mechanisms of sodium/water absorption in the intestine, and in which sections do they occur?

Na+/glucose co-transport- small intestine (post-prandial period).

Na+/amino acid co-transport- small intestine (post-prandial period).

Na+/H+ exchange- duodenum and jejunum.

Parallel Na+/H+ and Cl-/HCO3- exchange- ileum and colon (inter digestive period).

Epithelial Na+ channels (ENaC)- distal colon.

What are the 5 cellular mechanisms of Cl- absorption in the intestine, and in which sections do they occur?

Na+/glucose co-transport (Cl- also reabsorbed)- small intestine (post-prandial period).

Na+/amino acid co-transport (Cl- also reabsorbed)- small intestine (post-prandial period).

Epithelial Na+ channels (ENaC) (Cl- also reabsorbed)- large intestine (distal colon).

Parallel Na+/H+ and Cl-/HCO3- exchange- ileum and colon (inter digestive period).

Cl-/HCO3- exchange- ileum and colon.

Describe the cellular mechanism involved in Cl- secretion.

Cl- secretion occurs from crypt cells, and occurs at a basal rate but is usually overshadowed by a higher rate of absorption.

What is CFTR activated by?

Bacterial enterotoxins, hormones, neurotransmitters, immune cell products, some laxatives.

What is the role of CFTR (cystic fibrosis transmembrane regulator) in diarrhoea?

Cl- exits cells via CFTR on the apical membrane. This causes Na+ paracellular secretion and water secretion, resulting in secretory diarrhoea.

Describe secretory diarrhoea.

Toxin enters enterocyte enzymatically inhibits GTPase activity of GSA subunit. This results in increased activity of adenylate cyclase, increased concentration of cAMP. cAMP stimulates CFTR, resulting in hyper secretion of Cl-, with Na+ and water following. Most common cause is E. Coli and and cholera.

Cause of infectious diarrhoea?

Enterotoxins from some strains of E. Coli and campylobacter, salmonella,norovirus result in impaired absorption of NaCl.

Cause of exudative diarrhoea?

Inflammation and destruction of the intestinal absorptive epithelium.

Describe hypermotility in relation to diarrhoea.

Excessive peristalsis of the GI with reduced absorption of solutes and water (eg. Irritable bowel syndrome).

What is osmotic diarrhoea?

Non-absorbable or poorly absorbable solutes in intestinal lumen.

What are the consequences of diarrhoea?

Dehydration, metabolic acidosis (HCO3- loss), hypokalaemia (K+ loss).

How do opiates how anti-diarrhoeal activity?

They inhibit enteric neurones, decrease peristalsis, increase segmentation, increase fluid absorption, constriction pyloric and anal sphincters.

Describe the 3 ways in which lactose intolerance can occur?

Primary lactase deficiency- lack of lactase persistence (LP) allele- most common cause.

Secondary lactase deficiency- caused by damage to/infection of the proximal small intestine.

Congenital lactase deficiency (rare autosomal recessive disease)- no ability to digest lactose from birth.

Describe how the symptoms of lactose intolerance occur?

If lactose is not broken down and then is delivered from the colon to the ileum, colonic microflora produce short-chain fatty acids, hydrogen, carbon dioxide and methane. This results in bloating, abdominal pain and diarrhoea.

How is lactose intolerance diagnosed?

Association of symptoms with lactose consumption, hydrogen breath test, lactose/milk tolerance test.

Name some causes of constipation?

Neurogenic disorders of the large intestine leading to reduced peristalsis (eg. Megacolon, hypothyroidism, IBD, cancer).

Abdominal muscle weakness.

Diet poor of fibres.

Sedentary life style.

Constant suppression of the urge to empty.

Antidepressant drugs- anticholinergics.

Opiates.

Aging.

What changes in lifestyle can be made to treat constipation?

More water and less alcohol should be consumed, add wheat bran to the diet, increase exercise, improve toilet routine, don’t delay, rest feet on low stool while going to toilet.

What are the 4 purgative drugs that treat constipation?

Bulk laxatives (eg. Methylcellulose).

Osmotic laxatives (eg. Magnesium hydroxide, lactulose).

Faecal softeners (eg. Arachis oil, docusate sodium).

Stimulant laxatives (eg. Senna, Dantron).

What type of non-purgative drug can be used in the treatment of constipation?

Antiemetics- increase GI motility and gastric emptying.